Anti-endothelial properties of 1,25-dihydroxy-3-epi-vitamin D3, a natural metabolite of calcitriol

The Journal of Steroid Biochemistry and Molecular Biology
Paul Furigay, Narasimha Swamy

Abstract

Calcitriol [1,25-(OH)(2)D(3)] is a strong anti-proliferative agent both in vitro and in vivo. Earlier studies have established that calcitriol inhibits the growth factor-stimulated proliferation of endothelial cells (EC) and angiogenesis. However, the lethal calcemic side effects of calcitriol prohibit its use as a therapeutic agent. Several analogs of vitamin D have been developed to minimize these calcemic side effects. 1,25-dihydroxy-3-epi-vitamin D(3) (3-epiD(3)), a naturally formed vitamin D metabolite is one such analog. To demonstrate that 3-epiD(3), a calcitriol analog, inhibits endothelial cell proliferation and induces apoptosis. Treatment of EC with 3-epiD(3) showed 60% inhibition (P < 0.006) of proliferation. Cell viability assays corroborated these results. Pro-apoptotic caspase-3 activity was increased fourfold (P < 0.01) in 3-epiD(3)-treated cells over controls. 3-epiD(3) induced apoptosis in EC as shown by genomic DNA fragmentation. Cell cycle analysis of 3-epiD(3)-treated EC revealed a G0/G1 arrest. 3-epiD(3), a low-calcemic, natural analog of calcitriol, inhibits EC proliferation by causing a G0/G1 arrest and induces apoptosis more effectively than 1,25-(OH)(2)D(3). These results suggest that 3-epiD(3) is a po...Continue Reading

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Citations

Apr 10, 2015·Pharmaceutical Biology·Marco GiammancoGaetano Leto
Oct 15, 2013·The Journal of Steroid Biochemistry and Molecular Biology·Janice García-QuirozLorenza Díaz

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